Under normal conditions, the lymphatic network maintains fluid homeostasis by draining lymph fluid from extracellular spaces, absorbs lipids from the intestinal tract, and transports white blood cells and antigen- presenting cells to lymphoid organs. During infection, the lymphatic vasculature is the main route for the immune response, and in cancer, tumor cells migrate via the lymphatic vasculature to lymph nodes and distant organs. Malfunctions of the lymphatic system can lead to congenital or inherited disorders such as lymphedema, a disfiguring and disabling disorder that is caused by imbalance in lymph absorption and often characterized by swelling of the extremities. A better knowledge of the cellular and molecular features controlling normal lymphatic vasculature development should facilitate our understanding of pathologic lymphatic conditions that lead to inflammation, autoimmunity, cancer, and obesity and to improve the clinical treatment of primary and secondary forms of lymphedema. PUBLIC HEALTH RELEVANCE: Our understanding of the genes and mechanisms controlling the formation of the lymphatic vasculature has improved greatly during the last decade thanks to the availability of molecular markers and animal models with various degrees of lymphatic defects. This knowledge has helped us not only to improve our understanding of lymphatics-related pathologic conditions but also to re-evaluate the functional roles of the lymphatic vasculature in health and disease. Therefore, increasing our understanding of developmental lymphangiogenesis should keep impacting on our understanding of pathologic lymphatic conditions.